title: T-2 toxin is hydroxylated by chicken CYP3A37.
abstract: T-2 toxin (T-2) is an acute toxic trichothecene mycotoxin produced mainly by Fusarium species, detected in many crops including oats, wheat and barley, in animal feed and food. It is important to know the metabolic pathway and kinetics of T-2 in food animals given that T-2 can cause serious adverse effects on human health. In this study, we investigated the metabolic capacity of chicken CYP3A37 in the metabolism of T-2 using reconstituted bacteria produced enzymes. Our results showed that chicken CYP3A37 is able to convert T-2 to 3'-OH T-2 with an apparent Km of 15.29 μM, and T-2 hydroxylation activity of CYP3A37 is strongly inhibited by ketoconazole (IC50=0.11 μM). We also observed that chicken CYP3A37 can catalyze erythromycin N-demethylation, another CYP3A-specific activity. These findings imply that chicken CYP3A37 may have a broad substrate spectrum, similar to its human homologue CYP3A4.
authors.affiliation: State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Yuan
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zhou
authors.forename: Jiannan
authors.initials: J
authors.lastname: Yang
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Xinghui
authors.initials: X
authors.lastname: Qiu
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002645:Chickens; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D000072469:Cytochrome P450 Family 3; D015786:Cytochromes b5 / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D006900:Hydroxylation; D007654:Ketoconazole / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013605:T-2 Toxin / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D011994:Recombinant Proteins; D015786:Cytochromes b5; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D000072469:Cytochrome P450 Family 3; C465259:cytochrome P-450 CYP3A37 (chicken); D013605:T-2 Toxin; D007654:Ketoconazole
keywords: ACN; CID; CPR; CYP3A37; DMSO; ERND; ESI; Erythromycin N-demethylase; Gallus gallus; HPLC-Q-TOF/MS; Hydroxylation; NADPH; NEO; P450; T-2 toxin; acetonitrile; collision induced dissociation; cytochrome P450; cytochrome P450 reductase; dimethyl sulfoxide; electrospray ionization; erythromycin N-demethylase; high performance liquid chromatography-quadrupole time-of-flight mass spectrometry; neosolaniol; reduced nicotinamide adenine dinucleotide phosphate